Capreomycin - instructions for use, dose, side effects, contraindications

The polypeptide antibiotic produced Streptomyces capreolus. It has a bacteriostatic effect only on various strains Mycobacterium tuberculosis (the minimum inhibitory concentration is 1.25-2.5 mg / l on average when measured in a liquid medium). The mechanism of action of capreomycin is associated with the suppression of protein synthesis in a bacterial cell. Anti-tuberculosis drug of the II series (according to the classification of the World Health Organization).

With monotherapy capreomycin quickly causes the emergence of resistant strains of mycobacteria. Capreomycin has full cross-resistance with viomycin, partial cross-resistance - with some antibiotics-aminoglycosides (including with kanamycin and neomycin). There is no cross-resistance between capreomycin and isoniazid, aminosalicylic acid, cycloserine, streptomycin, ethionamide, ethambutol.

Capreomycin should be used only as part of complex therapy, as an anti-tuberculosis drug of the II series, incl.with inefficiency and intolerance of anti-tuberculosis drugs of the 1st series (isoniazid, rifampicin, pyrazinamide, streptomycin, ethambutol) and in the presence of sensitivity Mycobacterium of the patient to capreomycin and to simultaneously used other anti-tuberculosis drugs.

Capreomycin has a teratogenic effect (anomalies in the development of the skeleton in experiments on rats).

Pharmacokinetics:

Capreomycin is practically not absorbed in the gastrointestinal tract (less than 1%), therefore it is introduced into the body only parenterally. The maximum concentration in blood plasma CmAch is achieved 1-2 hours after intramuscular injection of 1 g capreomycin and is 20-47 mg / l; after 10 hours the concentration is 4 mg / l. After intravenous infusion of capreomycin for 1 hour at a dose of 1 g Cmax is 30-50 mg / l. The area under the "concentration-time" curve for intravenous and intramuscular injection is the same.

Capreomycin does not penetrate the blood-brain barrier, but penetrates the placental barrier.

In organism capreomycin not metabolized.

It is excreted mainly by the kidneys (within 12 hours - 50-60% of the dose) by glomerular filtration in unchanged form, in small amounts - with bile.

Capreomycin does not cumulate with a daily dose of 1 g for 30 days with normal kidney function. If the kidney function is impaired, the period forI'm losing momentum and there is a tendency to accumulation.

Indications:

As part of complex therapy - pulmonary tuberculosis, with ineffectiveness or intolerance of anti-tuberculosis drugs of the I series, as well as in resistance to them.

Contraindications:

Hypersensitivity, pregnancy, the period of breastfeeding, children's age.

Carefully:

Caution should be applied capreomycin in patients with renal insufficiency and already existing hearing impairments. If it is necessary to prescribe the drug in such cases, the ratio of the expected benefits of therapy and the risk of additional impairment of the function of the VIII pair of cranial nerves and damage to the kidneys.

With caution appoint capreomycin (as well as other antibiotics) to patients with any form of allergy, including drug.

During and after surgery, use with caution on the background of drugs that cause neuromuscular blockade (especially with a high probability of incomplete termination in the postoperative period).

Dehydration, myasthenia gravis gravis, Parkinsonism, old age.

Pregnancy and lactation:

Use during pregnancy is contraindicated.

During the use of the drug should be excluded breastfeeding

Dosing and Administration:

Before the beginning of therapy it is necessary to confirm the presence of a patient sensitive to capreomycin strain of Mycobacterium tuberculosis.

The average dose of capreomycin is 1 g / day, not more than 20 mg / kg / day.

Capreomycin is administered intramuscularly (deep) or intravenously (by dropwise infusion with a duration of 60 minutes) once a day for 60-120 days, and then - 1 g 2 or 3 times a week for 12-24 months in combination with other antituberculous preparations.

Patients with impaired renal function should reduce the dose in accordance with the creatinine clearance according to the following table:

Clearance toreatinin (ml / min)	Clearance capreomycin (l / kg / hr 10²)	Period half-life (clock)	Dose (mg / kg) for the following dosage intervals
Clearance toreatinin (ml / min)	Clearance capreomycin (l / kg / hr 10²)	Period half-life (clock)	24 hours	48 hours	72 hours
0	0,54	55,5	1,29	2,58	3,87
10	1,01	29,4	2,43	4,87	7,30
20	1,49	20,0	3,58	7,16	10,7
30	1,97	15,1	4,72	9,45	14,2
40	2,45	12,2	5,87	11,7
50	2,92	10,2	7,01	14,0
60	3,40	8,8	8,16
80	4,35	6,8	10,4
100	5,31	5,6	12,7
110	5,78	5,2	13,9

For intramuscular administration, the contents of the bottle are 0, 5 g, 0, 75 g, 1 g dissolved in 1 ml, 1.5 ml, 2 ml of 0.9% solution of sodium chloride or sterile water for injection (wait 2-3 min until complete dissolution of the powder).

With intramuscular injection capreomycin is injected deep into the muscle, as a superficial injection can cause increased soreness and development of aseptic abscesses.

For intravenous drip injection, the capreomycin solution prepared in the same way is dissolved in 100 ml of 0.9% sodium chloride solution and injected for 60 minutes.

To introduce a dose of 1 g, you must use the entire contents of the vial containing 1 g of the drug. To introduce a dose of less than 1 g of this vial, the following dilution table is recommended:

Table of dilutions

The amount of solvent added to a 10 ml vial containing a dose of 1 g	Volume of a solution of capreomycin	Concentration of solution (approx.)
2.15 ml	2.85 ml	370 mg / ml
2.63 ml	3.33 ml	315 mg / ml
3.3 ml	4 ml	260 mg / ml
4.3 ml	5 ml	210 mg / ml

A solution of capreomycin may acquire a pale straw color and eventually darken, but this is not accompanied by loss of activity or the appearance of toxicity. After dilution, the solution can be stored in the refrigerator for no more than 24 hours.

Side effects:

From the urinary system: nephrotoxicity (an increase in the level of urea nitrogen in the blood more than 20 mg / 100ml,decrease in the excretion of phenolsulfonphthalein and the appearance of an abnormal urinary sediment, electrolyte imbalance resembling Barter's syndrome and the development of toxic nephritis).

From the central nervous system: neurotoxicity, neuromuscular blockade.

From the sense organs: ototoxicity (subclinical hearing loss, tinnitus and dizziness).

From the side of the liver: violation of liver function tests with simultaneous treatment with capreomycin and other anti-tuberculosis drugs that cause changes in liver function.

Allergic reactions: with the simultaneous use of capreomycin and other anti-tuberculosis drugs - hives and skin eruptions in the form of spots and nodules, accompanied by a sometimes febrile reaction.

From the hematopoietic system: eosinophilia, leukocytosis, leukopenia, thrombocytopenia, hyperuricuria (more than 20 mg / 100 ml) cylindruria, hematuria, leukocyturia.

Local Reactions: pain and densification and increased bleeding at the injection site, aseptic abscess.

Overdose:

Symptoms: dizziness, tinnitus,Vertigo (defeat of the auditory and vestibular divisions of the VII pair of cranial nerves), a decrease in general tone, neuromuscular blockade (respiratory paralysis), hypokalemia, hypocalcemia, hypomagnesemia and electrolyte imbalance, acute necrosis of renal tubules.

Treatment: with normal kidney function - hydration with maintenance of urine at a level of 3-5 ml / h / kg; control of water balance, electrolyte level and creatinine clearance; for the removal of neuromuscular blockade - the introduction of cholinesterase inhibitors, calcium preparations; with severe renal dysfunction - hemodialysis.

Interaction:

The miorelaxing effect is enhanced by diethyl ether, aminoglycosides, polymyxins, citrated blood preservatives, reduced - neostigmine methylsulfate.

In combination with other anti-tuberculosis drugs (streptomycin, viomycin), and when combined with polymyxin, sodium colistimetate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, neomycin, furosemide, ethacrynic acid or methoxyfluorane, the ototoxic and nephrotoxic effect is mutually reinforced.

Special instructions:

Prior to treatment with capreomycin and regularly during treatment (1-2 times per week), audiometry and vestibular function evaluation should be performed.

The study of kidney function should be performed before treatment and once a week during treatment. It is recommended to monitor the concentration of the drug in the blood. During treatment, hematologic parameters and liver function are also monitored.

Damage to the kidneys, which can occur with the use of capreomycin, is accompanied by necrosis of the renal tubules, an increase in the level of urea nitrogen in the blood or serum creatinine, the appearance of a pathological sediment in the urine.

For elderly patients, patients with impaired renal function or dehydration and patients receiving other nephrotoxic drugs, the risk of developing acute necrosis of the renal tubules is much higher.

A slight increase in urea nitrogen and serum creatinine was observed in the majority of patients who received long-term therapy. Many of them noted the appearance in the urine of cylinders, erythrocytes and leukocytes. With an increase in the urea nitrogen level of more than 30 mg / 100 ml,as well as any other signs of a decrease in renal function with an increase in the level of urea nitrogen or without it, as well as in case of suspected renal dysfunction, a thorough examination of the patient, a dose reduction based on creatinine clearance or complete withdrawal of the drug is required.

Auditory and vestibular damage VIII pairs of cranial nerves occur more often in patients with impaired renal function or dehydration, as well as with the simultaneous use of drugs that have ototoxic effect. Such patients often experience dizziness and tinnitus.

After rapid intravenous injection of capreomycin, neuromuscular blockade or respiratory paralysis is possible.

Since hypokalemia may develop during treatment, the serum potassium content should be determined on a monthly basis.

During treatment, it is necessary to constantly monitor the regimen and dosage regimens, the correctness and regularity of the appointments. In the case of a miss, the injection is administered as soon as possible, only if the time of administration of the next dose has not come; Doses do not double.

Simultaneous reception with streptomycin viomycin Not recommended.

Effect on the ability to drive transp. cf. and fur:

During the use of the drug, care should be taken when driving vehicles, mechanisms and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection 500 mg, 750 mg, 1000 mg.

Packaging:

For 500, 750, 1000 mg capreomycin in 10 ml vials, hermetically sealed with rubber stoppers, crimped aluminum caps or caps combined aluminum with plastic caps.

1,5, or 10 bottles together with instructions for medical use are placed in a pack of cardboard.

50 bottles together with 5 instructions for use are placed in carton boxes for delivery to hospitals.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Store in placesah, inaccessible to children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000215

Date of registration:16.02.2011

The owner of the registration certificate:SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp16.02.2011

Illustrated instructions

Instructions

Capreomycin (Capreomycin)